Chronic stress induces signalling from the sympathetic nervous system through β-adrenoceptors to drives cancer progression. However, the pathways of tumour cell dissemination are unclear. To address this we used state-of-the-art intravital microscopy and preclinical models of cancer to investigate the effect of stress-induced β-adrenoceptor signalling on the formation of sub-cellular invasive structures and on remodelling of vascular routes of tumour cell dissemination. We show that chronic stress restructures lymphatic networks within and around tumours to provide pathways for tumour cell escape. Using functional cellular assays we show that β-adrenoceptor signalling increased both the frequency and number of invadopodia on tumour cells, which increased tumour cell invasion through extracellular matrix. Selective antagonism of β₂-adrenoceptors with beta-blocker drugs stopped invadopodia formation and prevented vascular remodelling, suggesting a pharmacological strategy to prevent tumour spread. These findings reveal unanticipated communication between stress-induced neural signalling and tumour cell dissemination. We are currently evaluating the clinical utility of β-adrenoceptor antagonism to stop cancer metastasis in a phase II double-blinded placebo-controlled study.